Metabolic surgery: the role of the gastrointestinal tract in diabetes mellitus

Abstract

Several conventional methods of bariatric surgery can induce long-term remission of type 2 diabetes mellitus (T2DM); novel gastrointestinal surgical procedures are reported to have similar effects. These procedures also dramatically improve other metabolic conditions, including hyperlipidemia and hypertension, in both obese and nonobese patients. Several studies have provided evidence that these metabolic effects are not simply the results of drastic weight loss and decreased caloric intake but might be attributable, in part, to endocrine changes resulting from surgical manipulation of the gastrointestinal tract. In this Review, we provide an overview of the clinical evidence that demonstrates the effects of such interventions-termed metabolic surgery-on T2DM and discuss the implications for future research. In light of the evidence presented here, we speculate that the gastrointestinal tract might have a role in the pathophysiology of T2DM and obesity.

Figure 1

Conventional bariatric operations. a During laparoscopic adjustable gastric banding, the upper part of the stomach is encircled by a saline-filled tube. The extent of restriction can be adjusted by injecting/withdrawing saline solution to/from the tube. b During Roux-en-Y gastric bypass, a surgical stapler is used to create a small, vertical gastric pouch. The upper pouch, which is completely separated from the gastric remnant, is anastomosed to the jejunum, whereas the excluded biliary limb is anastomosed to the alimentary limb. After surgery, ingested food bypasses about 95% of the stomach, the entire duodenum and a portion of the jejunum, but bile and nutrients mix in the distal jejunum and can be absorbed through the remaining portion of the small bowel. Biliopancreatic diversion involves a horizontal resection (c) or a vertical resection (d, also known as ‘sleeve gastrectomy’ or ‘duodenal switch’). The reduced stomach is anastomosed to the distal 250 cm of the small intestine. The excluded small intestine, which carries the bile and pancreatic secretions, is connected to the alimentary limb. Bile and nutrients mix in a short segment of small bowel, the only site where fat and starches are absorbed; noncaloric nutrients are absorbed in the alimentary limb.

Figure 2

Novel methods of metabolic surgery. a Duodenal–jejunal bypass consists of a stomach-preserving bypass of a short segment of proximal small intestine (similar to that bypassed in a standard Roux-en-Y gastric bypass). Some variants of this procedure preserve the pylorus. This procedure might be associated with a sleeve resection of the stomach, which reduces the risk of marginal ulcerations and increases weight loss (b). Long-term data about the efficacy of this procedure are not yet available. c Sleeve gastrectomy not only reduces the capacity of the stomach but also eliminates the ghrelin-rich gastric fundus, which might contribute to the beneficial effects of the procedure. Sleeve gastrectomy has been also shown to improve type 2 diabetes mellitus in patients with severe obesity. The efficacy of the procedure in the long-term needs to be further investigated. d During ileal interposition, a small segment of ileum (with its intact vascular and nervous supplies) is surgically interposed into the proximal small intestine, which increases its exposure to ingested nutrients. Ileal interposition can be performed alone or in association with sleeve gastrectomy and duodenal exclusion. The procedure requires three anastomoses (gastric bypass operations include two). The long-term effects of this procedure are unknown.

Figure 3

Intestinal factors that contribute to the pathophysiology of T2DM. A dysfunctional intestinal signal is posited to be involved in the pathophysiology of T2DM. According to this hypothesis, overstimulation of the gastrointestinal tract (by overeating and/or the presence of chemical or biological stimuli in modern diets) could lead to insulin resistance, obesity and T2DM, whereas all forms of restriction of nutrients’ transit could improve these conditions. Indeed, diet might improve T2DM not just because of a restriction of caloric intake, but owing to the reduced stimulation of abnormal intestinal mechanisms. Likewise, restrictive surgery could improve T2DM by reducing the nutrient load even further. Bypass operations, which completely and indefinitely inactivate a large part of the intestine, reduce nutrient-related stimuli more than any other approach and are the most effective ways of improving T2DM, obesity and insulin resistance syndrome. Abbreviation: T2DM, type 2 diabetes mellitus.